Compositions and methods for treating cancer

Abstract

Provided are compositions and methods of treating subjects having cancer which involve administering to the subject an anti-PD-L1 or an anti-PD-1 antibody and an inhibitor of cyclin D kinase (CDK)4/6 to treat the cancer. Combining CDK4/6 inhibitor treatment with anti-PD-L1 or anti-PD-1 immunotherapy enhanced tumor regression and dramatically improved overall survival rates in tumor models.

1 . A therapeutic combination comprising a cyclin D kinase 4/6 (CDK4/6) inhibitor and an anti-PD-L1 antibody and/or an anti-PD-1 antibody. 
     
     
         2 . The therapeutic combination of  claim 1 , wherein the CDK4/6 inhibitor is palbociclib, ribociclib, abemaciclib or trilaciclib. 
     
     
         3 . The therapeutic combination of  claim 1 , wherein the anti-PD-1 antibody is nivolumab, pembrolizumab, or pidilizumab. 
     
     
         4 . The therapeutic combination of  claim 1 , wherein the anti-PD-L1 antibody is MPDL3280A, MEDI4736, BMS-936559, or MSB0010718C. 
     
     
         5 . The therapeutic combination of  claim 1 , wherein the combination comprises a CDK4/6 inhibitor and an anti-PD-L1 or an anti-PD-1 antibody. 
     
     
         6 . The therapeutic combination of  claim 1 , wherein the combination is formulated in a single composition or is formulated and administered separately. 
     
     
         7 . The therapeutic combination of  claim 1 , wherein the combination comprises a CDK4/6 inhibitor and an anti-PD1 antibody. 
     
     
         8 . The therapeutic combination of  claim 1 , wherein the CDK4/6 inhibitor is palbociclib. 
     
     
         9 . A method of reducing tumor growth, the method comprising contacting a tumor cell with a cyclin D kinase 4/6 (CDK4/6) inhibitor and an anti-PD-L1 and/or an anti-PD-1 antibody, thereby reducing tumor growth. 
     
     
         10 . A method of treating cancer in a subject, the method comprising administering to the subject a cyclin D kinase 4/6 (CDK4/6) inhibitor and an anti-PD-L1 and/or an anti-PD-1 antibody, thereby treating cancer in the subject. 
     
     
         11 . The method of  claim 9 , wherein the CDK4/6 inhibitor is palbociclib, ribociclib, abemaciclib, or trilaciclib. 
     
     
         12 . The method of  claim 9 , wherein the anti-PD-1 antibody is nivolumab, pembrolizumab, or pidilizumab. 
     
     
         13 . The method of  claim 9 , wherein the anti-PD-L1 antibody is MPDL3280A, MEDI4736, BMS-936559, or MSB0010718C. 
     
     
         14 . The method of  claim 9 , wherein the combination comprises a CDK4/6 inhibitor and an anti-PD-L1 or an anti-PD-1 antibody. 
     
     
         15 . The method of  claim 9 , wherein the combination is formulated in a single composition or is formulated and administered separately. 
     
     
         16 . The method of  claim 7 , wherein the cancer is selected from the group consisting of colon cancer, breast cancer, melanoma, prostate cancer, lung cancer, and head and neck cancer. 
     
     
         17 . The method of  claim 7 , wherein treatment reduces tumor growth relative to a reference. 
     
     
         18 . The method of  claim 8 , wherein treatment increases survival of the subject. 
     
     
         19 . A kit comprising the therapeutic combination of  claim 1 .